Ultraviolet light is one of the major environmental factors to which humans are exposed and is known to be a significant cause of human skin cancer. Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce several types of cancers in humans and rodents. NSAIDs are believed to act by inhibiting the cyclooxygenases (COX), and we have observed that both COX-1 and COX-2 deficiencies reduce papilloma formation by about 80% in the initiation/ promotion model with the data suggesting that altered keratinocyte differentiation may be responsible. Our preliminary studies with UV indicate that mice deficient in COX-2, but not COX-1, exhibit dose dependent increases in apoptosis which are up to 5-fold elevated compared to COX-1 null or wild type mice and that this increased apoptosis could result in a reduced tumorigenic response.